Cancer is a class of disease caused by a failure of the controls that normally govern cell proliferation, differentiation and cell survival. Cells that undergo malignant transformation escape normal growth controls, invade surrounding tissue and may ultimately migrate to other sites in the body to establish secondary tumors. Cancer therapy typically involves surgery (for solid tumors) followed by cytotoxic drugs or radiation, either alone or in combination, to kill the cancer cells. An ongoing quest in detecting and treating cancer has been to find ways of educating the body's immune system to mount an orchestrated effort to kill cancer cells by activating the humoral and cellular immune systems to specifically attack growing cancer cells and spare the normal cells necessary for life.
One proposed method to treat cancer is to educate antigen-presenting cells, such as dendritic cells. Dendritic cells are immune cells that form part of an animal's immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells. They act as messengers between the innate and adaptive immunity. Dendritic cells are present in small quantities in an immature state in the blood. Once activated, they migrate to the lymphoid tissues where they interact with T and B lymphocytes to initiate and shape the adaptive immune response. Dendritic cells can be isolated and purified from animals.
Another proposed method to treat cancer is to directly educate T lymphocytes, part of the immune response necessary for activation of cellular immunity.
One strategy to treat cancer has been to insert the genetic contents of growing malignant tumors into the dendritic cells using flow electroporation. One application for flow electroporation is to use this technology to take malignant cells, removed from growing tumors in patients, and inserting them (or their lysed contents) into dendritic cells. This results in the education of dendritic cells such that when they are returned to the donor, both cellular and humoral immune responses are mounted to attack the malignant cells. A limitation of this process is the availability of malignant cells to electroporate into the dendritic cells of the donor. This requires a biopsy of the cancerous tissue, with inherent problems of surgery for biopsy, the inability to ensure that the biopsy contains relevant malignant tissue samples, and many types of cancers are not amenable to biopsy.
Previous studies have shown that cancer cells shed small packages of genetic information from growing tumors, called exosomes. Exosomes secreted by cells under normal and pathological conditions contain proteins, DNA and functional RNA molecules including mRNA and miRNA, which can be shuttled from one cell to another, affecting the recipient cell's protein production. Tumor exosomes are distinct from exosomes shed by normal cells. They are more abundant in cancer patients and they have an important role in the increased tumor growth, angiogenesis and the escape from the immune-surveillance. (Nilsson et al., Br J Cancer (2009) 100: 1603-1607). Genetic material and proteins contained within exosomes are the biological fingerprints of their malignant source cells.
Thus, there exists a need in the art for novel compositions and methods of use to treat cancer by directing the animal's own immune system to the cancer cells.